Cause of pleuroparenchymal fibroelastosis following allogeneic hematopoietic stem cell transplantation.

Late-onset noninfectious pulmonary complications (LONIPCs) are life-threatening complications after hematopoietic stem cell transplantation (HSCT). Pleuroparenchymal fibroelastosis (PPFE) is a LONIPC, but its etiology remains elusive. Chronic graft-versus-host disease (cGVHD) and alkylating agents used for conditioning have been considered possible causes of PPFE. Therefore, to investigate the primary cause of PPFE in allogeneic HSCT, we compared three secondary PPFE groups, namely, the post-lung-transplantation, post-autologous-HSCT or chemotherapy-alone, and post-allogeneic-HSCT groups, and focused on the coexistence of bronchiolitis obliterans (BO), a typical phenotype of cGVHD. We found a trend towards higher rates of PPFE with BO in the post-allogeneic-HSCT and post-lung-transplantation groups (71% and 90%, respectively) than in the post-autologous-HSCT or chemotherapy-alone group (25%). The incidence of BO following allogeneic HSCT is reportedly <10%. If PPFE in the post-allogeneic-HSCT group has no association with BO and is induced by alkylating agents rather than cGVHD, the incidence of BO in PPFE in this group is estimated to be <10%, which is inconsistent with our data (71%). Thus, this study suggests that PPFE following allogeneic HSCT could be mainly induced by cGVHD because the majority of cases are associated with BO, a typical phenotype of cGVHD.